Role played by the programmed death-1-programmed death ligand pathway during innate immunity against Mycobacterium tuberculosis

J Infect Dis. 2010 Aug 15;202(4):524-32. doi: 10.1086/654932.


Tuberculous pleurisy allows the study of specific cells at the site of Mycobacterium tuberculosis infection. Among pleural lymphocytes, natural killer (NK) cells are a major source of interferon gamma (IFN-gamma), and their functions are regulated by activating and inhibitory receptors. Programmed death-1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are recognized inhibitory receptors in adaptive immunity, but their role during innate immunity remains poorly understood. We investigated the PD-1:PD-L1/PD-L2 pathway on NK cell effector functions in peripheral blood and pleural fluid from patients with tuberculosis. M. tuberculosis stimulation significantly up-regulated PD-1, PD-L1, and PD-L2 levels on NK cells. Interestingly, a direct correlation between PD-1 and IFN-gamma expression on NK cells was observed. Moreover, blockade of the PD-1 pathway markedly augmented lytic degranulation and IFN-gamma production of NK cells against M. tuberculosis. Furthermore, PD-1(+) NK cells displayed a diminished IFN-gamma mean fluorescence intensity, denoting the relevance of PD-1 on IFN-gamma regulation. Together, we described a novel inhibitory role played by PD-1:PD-L interactions in innate immunity in tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / immunology*
  • Apoptosis Regulatory Proteins / immunology*
  • Apoptosis*
  • B7-H1 Antigen
  • Blood / immunology
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate*
  • Intercellular Signaling Peptides and Proteins / immunology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology
  • Mycobacterium tuberculosis / immunology*
  • Pleura / immunology
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Tuberculosis / immunology*
  • Tuberculosis / pathology*
  • Up-Regulation


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • Intercellular Signaling Peptides and Proteins
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Interferon-gamma